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There were significant differences in body weight gain and reproductive organ/body weight loss in rats feed with a HFD compared with control rats (P < 0.05; Figure 1 and Table 1). 4-PBA treatment significantly attenuated HFD‑induced body weight increases and seminal vesicle weight loss (P < 0.05; Figure 1 and Table 1). 4-PBA treatment also showed a tendency to alleviate HFD‑induced organ weight loss of epididymis and testis, but there were no statistically significant differences between the two groups (Figure 1 and Table 1).
Table 1. Effect of HFD Exposure and Supplementation with 4-PBA on Final Body Weights and Reproductive Organ/Body Weight Ratios (n = 10)
Parameter Control HFD HFD+4-PBA Final body weight (g) 534.00 ± 59.03 695.10 ± 41.58* 604.20 ± 51.00*# Seminal vesicle weight/BW (%) 0.36 ± 0.12 0.25 ± 0.04* 0.32 ± 0.06# Epididymis weight/BW (%) 0.26 ± 0.06 0.20 ± 0.02* 0.23 ± 0.03 Testis weight/BW (%) 0.69 ± 0.12 0.53 ± 0.07* 0.59 ± 0.07* Note. *P < 0.05 vs. control and #P < 0.05 vs. HFD; BW: body weight. -
Serum T levels were decreased significantly in the HFD-fed group compared with the control group (P < 0.05; Table 2). However, 4-PBA treatment for 13 weeks significantly ameliorated the HFD‑induced abnormal serum T levels (P < 0.05; Table 2). There were no significant differences in the levels of FSH and LH between the HFD-fed group and the control group. However, a significant difference between serum LH levels of the 4-PBA treatment group and the control group was observed (P < 0.05; Table 2).
Table 2. Effect of HFD Exposure and Supplementation with 4-PBA on Serum Hormones and Sperm Parameters (n = 10)
Parameter Control HFD HFD+4-PBA FSH (mIU/mL) 3.68 ± 0.96 3.88 ± 0.80 3.39 ± 0.77 LH (mIU/mL) 10.24 ± 2.03 8.74 ± 2.37 8.48 ± 1.52* T (ng/mL) 3.65 ± 0.75 2.50 ± 0.51* 3.16 ± 0.68# Sperm Concentration (106/mL) 57.80 ± 6.89 47.67 ± 4.80* 53.30 ± 3.16# Sperm viability (%) 95.60 ± 2.76 91.89 ± 4.14* 97.50 ± 1.43# Sperm motility (%) 67.70 ± 3.37 53.44 ± 4.03* 68.20 ± 3.01# Sperm abnormalities (%) 13.00 ± 3.37 21.00 ± 2.91* 12.60 ± 2.99# Note.*P < 0.05 vs. control and #P < 0.05 vs. HFD. -
Compared with the control, sperm parameters such as concentration, sperm viability, and motility were decreased significantly in rats subjected to a HFD diet (P < 0.05; Table 2). 4-PBA treatment significantly attenuated HFD‑induced impairment of spermatogenesis (P < 0.05; Table 2).
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Following 13 weeks of HFD feeding, rats in the HFD-fed group had significantly decreased testis weight/body ratios compared with the control group (P < 0.05; Table 1), which was also confirmed by analysis of histological changes in the testes (Figure 2). In the control group, the testicular structure consisted of abundant seminiferous tubule cells arranged normally and filled with numerous aligned spermatogenetic cells. As shown in Figure 2, atrophic seminiferous tubules, more vacuoles and decreased numbers of spermatogenic cell were observed in the HFD-fed group. However, 4-PBA treatment attenuated extenuated the testicular tissue damage caused by the HFD (Figure 2).
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TUNEL analysis was used to investigate the apoptosis rate of germ cells in the testis (Figure 3). The results revealed that rats in the HFD group had a significantly higher rate of apoptosis compared with control rats and that 4-PBA significantly inhibited HFD‑induced testicular cell apoptosis (P < 0.05; Figure 4).
doi: 10.3967/bes2018.118
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Abstract:
Objective To determine the mitigating effects of sodium 4-phenylbutyrate (4-PBA) on high-fat diet (HFD)-induced spermatogenesis dysfunction. Methods Male rats (n=30) were randomly divided into three groups:control, HFD, and 4-PBA (HFD +4-PBA). After 13 weeks, rats were euthanized. Testes and epididymis were harvested for further analysis. Sex hormones were detected, and hematoxylin and eosin staining was performed to examine the histological changes in the testes. Semen samples were collected to evaluate sperm quality. Spermatogenic cell apoptosis was detected by TUNEL assay. Results Compared with the control group, the final body weight and body weight gain were significantly higher in HFD-fed rats, while the testicle/body weight ratios were lower (P < 0.05). In HFD-fed rats, obvious pathological changes in the testicular tissue were observed. Treatment with 4-PBA attenuated HFD-induced histological damage, ameliorated the HFD-induced decrease in serum testosterone (T), and reduced the rate of testicular cell apoptosis (P < 0.05) in obese male rats. Finally, 4-PBA significantly improved semen parameters in HFD rats (P < 0.05). Conclusion HFD exposure induced detrimental effects on spermatogenesis, semen quality, serum T level, and testicular cell apoptosis in rats. Treatment with 4-PBA ameliorated HFD induced impaired spermatogenesis via inhibition of apoptosis in rats. 4-PBA may have therapeutic value in the treatment of obesity related impairment of spermatogenesis. -
Key words:
- Male infertility /
- Sodium 4-phenylbutyrate /
- Obesity /
- Spermatogenesis /
- Semen /
- Testis
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Table 1. Effect of HFD Exposure and Supplementation with 4-PBA on Final Body Weights and Reproductive Organ/Body Weight Ratios (n = 10)
Parameter Control HFD HFD+4-PBA Final body weight (g) 534.00 ± 59.03 695.10 ± 41.58* 604.20 ± 51.00*# Seminal vesicle weight/BW (%) 0.36 ± 0.12 0.25 ± 0.04* 0.32 ± 0.06# Epididymis weight/BW (%) 0.26 ± 0.06 0.20 ± 0.02* 0.23 ± 0.03 Testis weight/BW (%) 0.69 ± 0.12 0.53 ± 0.07* 0.59 ± 0.07* Note. *P < 0.05 vs. control and #P < 0.05 vs. HFD; BW: body weight. Table 2. Effect of HFD Exposure and Supplementation with 4-PBA on Serum Hormones and Sperm Parameters (n = 10)
Parameter Control HFD HFD+4-PBA FSH (mIU/mL) 3.68 ± 0.96 3.88 ± 0.80 3.39 ± 0.77 LH (mIU/mL) 10.24 ± 2.03 8.74 ± 2.37 8.48 ± 1.52* T (ng/mL) 3.65 ± 0.75 2.50 ± 0.51* 3.16 ± 0.68# Sperm Concentration (106/mL) 57.80 ± 6.89 47.67 ± 4.80* 53.30 ± 3.16# Sperm viability (%) 95.60 ± 2.76 91.89 ± 4.14* 97.50 ± 1.43# Sperm motility (%) 67.70 ± 3.37 53.44 ± 4.03* 68.20 ± 3.01# Sperm abnormalities (%) 13.00 ± 3.37 21.00 ± 2.91* 12.60 ± 2.99# Note.*P < 0.05 vs. control and #P < 0.05 vs. HFD. -
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